High resolution depth-encoding pet detector with prismatoid light guide array

ABSTRACT

Provided is a particle detection device and method of fabrication thereof. The particle detection device includes a scintillator array that includes a plurality of scintillator crystals; a plurality of detectors provided on a bottom end of the scintillator array; and a plurality of prismatoids provided on a top end of the scintillator array. Prismatoids of the plurality of prismatoids are configured to redirect particles between top ends of crystals of the scintillator array. Bottom ends of a first group of crystals of the scintillator array are configured to direct particles to a first detector of the plurality of detectors and bottom ends of a second group of crystals of the scintillator array are configured to direct particles to a second detector substantially adjacent to the first detector.

PRIORITY

This application is a continuation of U.S. application Ser. No.16/899,636, filed with the U.S. Patent and Trademark Office on Jun. 12,2020 which is a continuation of International Application No.PCT/US2020/018309, filed with the U.S. Patent and Trademark Office onFeb. 14, 2020, and claims benefit of U.S. Provisional PatentApplications Nos. 62/806,035 and 62/915,676 filed with the U.S. Patentand Trademark Office on Feb. 15, 2019 and Oct. 16, 2019, respectively,the entire contents of each which is incorporated herein by reference.

GOVERNMENT SUPPORT

This invention was made with government support under grant numberEB024849 awarded by the National Institutes of Health. The governmenthas certain rights in the invention.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates generally to the field of radiationimaging and, in particular, to positron emission tomography (PET).

2. Description of the Related Art

Molecular imaging with PET is a powerful technique used primarily fordiagnosis, treatment selection, treatment monitoring and research incancer [1] and neuropsychiatric disorders [2]. Despite its highmolecular specificity, quantitative nature and clinical availability,PET has not been able to achieve its full potential as the go-tomolecular imaging modality due in large part to its relatively poorspatial resolution, currently on the order of 3-6 mm [3,4]. With thiskind of spatial resolution, it is not possible to measure target densityin small nodules and in many human and rodent brain regions relevant todisease etiology and pathophysiology.

Depth-encoding PET detector modules have been developed to mitigateparallax error (mispositioning of the line of response) for longscintillator crystals [5]. This enables small diameter PET rings withreduced component cost per detector ring, large solid angle coverage forincreased sensitivity, and reduced contribution of annihilation gammaray acollinearity on spatial resolution when using crystals with smallcross-sectional area [4,6]. In addition, depth-of-interaction (DOI)information can be used to deconvolve optical photon transport in longcrystals, thus improving timing resolution [7,8]. Depth-encodingdetectors based on dual-ended readout achieve the best continuous DOIresolution of <2 mm [9,10]. High resolution PET systems such asmammography dedicated Clear-PEM have been developed using dual-ended DOIreadout detectors [11], but these systems are too costly to becommercialized due to the large number of readout electronics comparedto standard single-ended readout PET scanners. A recently developed highresolution variant of these detectors shows relatively poor energy andtiming resolutions due to the use of glass light guides at thecrystal-readout interface, which are required to achieve accuratecrystal identification [12]. Alternative single-ended readout detectormodules have been proposed to obtain DOI information such as multi-layerphoswich blocks [13,14], retroreflectors for modules with monolithicscintillators [15], and other custom reflector designs [16,17]. However,in all these designs tradeoffs exists among depth-encoding, cost,scintillator-to-readout coupling ratio, crystal identification accuracy,energy resolution, and timing resolution. To mitigate these tradeoffs,an ideal depth-encoding detector module is one with single-ended readoutwhere the crystal array is directly coupled to silicon photomultiplier(SiPM) pixels, without any intermediate glass light guide, to minimizesharing of downward traveling scintillation photons across multiplepixels and retain good timing resolution. In addition, upward travelingphotons, which do not contribute to the timing information, should beredirected via 180° bending of their paths towards the nearestneighboring SiPMs to retain good energy and DOI resolutions and mimicthe behavior of dual-ended depth-encoding readout detectors.

Accordingly, detector modules consisting of depolished multicrystalscintillator arrays coupled 4-to-1 to SiPM pixels on one side and auniform glass light guide on the opposite side have recently beeninvestigated in efforts to develop a practical and cost-effective highresolution time-of-flight (TOF) PET scanner, as well as achievecontinuous DOI localization using single-ended readout [8,18,19]. See,U.S. Pat. No. 10,203,419 to Frazao et al., the contents of which areincorporated herein by reference. In these detector modules, energyweighted average method is utilized for crystal identification toachieve energy and DOI resolutions of 9% and 3 mm full width at halfmaximum (FWHM), respectively, using 1.53×1.53×15 mm³ crystals and 3×3mm² SiPM pixels [8]. However, these arrays suffer from poor crystalidentification along their edges and corners due to the lack of lightsharing neighbors [19], an issue that must be addressed since the edgeand corner pixels comprise 75% and 44% of 4×4 and 8×8 SiPM readoutchips, respectively. Also, intercrystal light sharing is inefficientwhen using a uniform glass light guide since many upward travelingphotons are reflected back into the primary column and the rest areisotropically shared with a Gaussian intensity distribution amongstneighbors. The problem with isotropic light sharing is the distributionof low-intensity signal across many SiPMs, the integrity of which willbe severely affected by dark counts, resulting in degraded energy andDOI resolutions.

SUMMARY OF THE INVENTION

To overcome shortcomings of conventional systems, a particle detectorand a method for operation of same are provided herein based on aprismatoid PET (Prism-PET) detector module.

Accordingly, aspects of the present invention address the above problemsand disadvantages and provide the advantages described below. An aspectof the present invention provides a particle detection device thatincludes a scintillator array comprising a plurality of scintillatorcrystals, a plurality of detectors provided on a bottom end of thescintillator array, and a plurality of prismatoids provided on a top endof the scintillator array. Each prismatoid of the plurality ofprismatoids is configured to redirect particles between top ends ofcrystals of the scintillator array. Bottom ends of a first group ofcrystals of the scintillator array are configured to direct particles toa first detector of the plurality of detectors, and bottom ends of asecond group of crystals of the scintillator array are configured todirect particles to a second detector substantially adjacent to thefirst detector.

An aspect of the present disclosure provides a particle detector thatincludes a scintillator array comprising a plurality of scintillatorcrystals, a plurality of detectors provided on a bottom end of thescintillator array, a plurality of prismatoids provided on a top end ofthe scintillator array, and at least one processor in operativecommunication with the plurality of detectors. The at least oneprocessor comprises a plurality of supervised machine learningalgorithms configured to perform 3D gamma ray localization of at leastone interaction site within at least one scintillator crystal of theplurality of scintillator crystals.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other aspects, features and advantages of certainembodiments of the present invention will be more apparent from thefollowing detailed description taken in conjunction with theaccompanying drawings, in which:

FIG. 1 illustrates a uniform glass light guide module and distributionof light using same in a known detection system,

FIG. 2 illustrates detector modules with a specialized pattern ofsegmented prismatoid light guide according to embodiments of the presentdisclosure,

FIG. 3 illustrates distribution of light simulated in TracePro using themodule illustrates in FIG. 1,

FIG. 4 illustrates distribution of light simulated in TracePro using themodules illustrated in FIG. 2 according to embodiments of the presentdisclosure,

FIG. 5 illustrates arrangements of 4-to-1 coupled Prism-PET moduleaccording to embodiments of the present disclosure,

FIG. 6 provides perspective views providing details of the prismatoidarray, according to embodiments of the present disclosure,

FIG. 7 illustrates arrangements of 9-to-1 coupled Prism-PET module,according to embodiments of the present disclosure,

FIG. 8 provides perspective views of a light guide array, according toembodiments of the present disclosure,

FIG. 9 illustrates a detector readout for 4-to-1 with uniform glass inaccordance with known detector module,

FIG. 10 illustrates a detector readout of 4-to-1 coupled Prism-PETmodule, according to embodiments of the present disclosure,

FIG. 11 illustrates a detector readout of 9-to-1 coupled Prism-PETmodule, according to embodiments of the present disclosure,

FIG. 12 provides crystal identification histograms based on centroidingand measured energy histograms with and without DOI filtering, comparingresults of a detector readout for 4-to-1 with uniform glass inaccordance with known detector module and results using detector modulesaccording to embodiments of the present disclosure,

FIG. 13A provides DOI resolution of the uniform glass light guide moduleof known detector module, FIG. 13B provides DOI resolution of 4-to-1coupled Prism-PET module according to embodiments of the presentdisclosure and FIG. 13C provides a comparison of DOI resolution of thetwo,

FIGS. 14A-14D provide measured DOI resolution graphs of the 4-to-1coupled Prism-PET module, according to embodiments of the presentdisclosure,

FIGS. 15A-15D provide sensitivity graphs and dimensions of severaldifferent PET scanners, according to embodiments of the presentdisclosure,

Please amend page 5, lines 1-3 as follows:

FIGS. 16A-16F illustrate theoretical light distribution for aside-by-side Compton interaction in the 4-to-1 coupled Prism-PET module,according to embodiments of the present disclosure, and

FIG. 17 illustrates photoelectric and Compton interaction measurementsin the 4-to-1 coupled Prism-PET module, according to embodiments of thepresent disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The following detailed description of certain embodiments of the presentinvention will be made with reference to the accompanying drawings. Indescribing the invention, explanation about related functions orconstructions known in the art are omitted for the sake of clearness inunderstanding the concept of the invention, to avoid obscuring theinvention with unnecessary detail.

Disclosed herein are single-ended readout depth-encoding detectormodules that utilize specialized patterns of segmented prismatoid lightguides. Among the features of the Prism-PET detector modules disclosedin the various embodiments, at least three distinct prismatoid designsare utilized, i.e. a center prismatoid, an edge prismatoid, and a cornerprismatoid, with each of the center prismatoid, the edge prismatoid, andthe corner prismatoid being of different predefined design to mitigateedge and corner artifacts, thus achieving uniform crystal identificationperformance.

Intercrystal light sharing is confined to only crystals belonging tonearest SiPM neighbors to create a deterministic and anisotropicintercrystal light sharing pattern and maximize signal-to-backgroundratio on those SiPMs to improve both energy and DOI resolutions.

The segmentation pattern improves crystal identification by decouplingadjacent crystals that would otherwise have similar readout patterns,with the shape of each prismatoid being interchangeable, withembodiments of the prismatoid being substantially shaped as at least oneof at least one prism, at least one antiprism, at least one frustum, atleast one triangle, at least one cupola, at least one parallelepiped, atleast one wedge, at least one pyramid, at least one truncated pyramid,at least one portion of a sphere, at least one cuboid, and at least onepyramid. For ease of reference, right triangular prisms are discussedherein, with the right triangular prisms enhancing intercrystal lightsharing ratios, thus improving both crystal identification and DOIresolution.

When optical photons enter the hypotenuse of the right triangularprisms, the optical photons undergo 180° deviation, efficiently guidingthem to neighboring crystals which are coupled to different readoutpixels due to the offset crystal-to-prism coupling scheme with respectto crystal-to-pixel coupling, as illustrated in FIGS. 1-8.

FIG. 1 illustrates a uniform glass light guide module of a knowndetector module and FIG. 3 illustrates the distribution of light usingsame, simulated in TracePro. FIG. 2 illustrates detector modules with aspecialized pattern of segmented prismatoid light guide according toembodiments of the present disclosure.

FIG. 4, which illustrates the distribution of light using the detectormodules in FIG. 2, simulated in TracePro, shows the confining lightsharing to an array of 16×16 crystals 120 coupled to the sameprismatoid, thereby enhancing intercrystal light sharing ratios, for thePrism-PET of embodiments of the present disclosure.

FIG. 5 illustrates arrangements of 4-to-1 coupled Prism-PET moduleaccording to embodiments of the present disclosure. The lower leftcorner of FIG. 5 is a plan view illustrating the relative arrangement of2×2 crystals of a scintillator array comprising a plurality ofscintillator crystals and SiPM pixels 140 of a plurality of detectorsprovided on a bottom end of the scintillator array. The upper rightcorner of FIG. 5 illustrates three distinct prismatoid designs beingutilized in the embodiment of FIG. 5, with the center prismatoid 162,the edge prismatoid 168, and the corner prismatoid 166 having adifferent design for mitigating edge and corner artifacts, thusachieving uniform crystal identification performance. As illustrated inFIG. 6, the three distinct prismatoids are provided in a predefinedarrangement on a top end 122 of the scintillator array, and areconfigured to redirect particles between top ends of crystals of thescintillator array.

Different Prism-PET detector modules were fabricated for comparison. Afirst Prism-PET detector 142 consisted of a 16×16 array of 1.4×1.4×20mm³ lutetium yttrium orthosilicate (LYSO) crystals coupled 4-to-1 on oneside to an 8×8 SiPM readout array 140 and on the opposite(radiation-receiving) side to a uniform glass light guide, similar tomodules previously studied in the literature [8,20]. A second Prism-PETdetector 144 consisted of the same crystal and readout geometry, theconventional single uniform glass light guide was interchanged with aprismatoid light guide array having unique design and layout of prismsat the corner, edge, and center of the detector module to optimize lightsharing patterns (FIGS. 5-8). A third Prism-PET detector had theprismatoid light guide array and used the same SiPM array as the otherdetectors but utilized an ˜24×24 array of 0.96×0.96×20 mm³ LYSO crystalsto achieve 9-to-1 coupling (FIG. 7 and FIG. 8). In both Prism-PETdetector modules, scintillator crystals are coupled to readout pixelsand right triangular prisms in equal ratios.

The coupling scheme of the prisms is offset from that of the readoutpixels, such that each crystal is only coupled to other crystalsbelonging to different readout pixels (FIG. 5). When optical photonsenter the prismatoids following gamma ray interactions in the crystals,the photons (i.e. particles 300) are efficiently redirected toneighboring crystals due to the right triangular prism geometry,enhancing the light sharing ratio between pixels (FIG. 2). The geometryof each prismatoid is position dependent and predefined to decoupleadjacent crystals along edges and corners that would otherwise havesimilar readout patterns in order to optimize crystal separation. Incertain embodiments of the present disclosure, a first group comprisesfour crystals and a second group comprises four crystals, and the firstgroup and the second group share two adjacent crystals of the fourcrystals. In certain embodiments, only the shared crystals areconfigured to direct particles to both the first detector and the seconddetector.

As illustrated in FIGS. 7 and 8, a first prismatoid 162 of the pluralityof prismatoids is configured to redirect particles between top ends 122of a group of nine crystals of the scintillator array 120. Inembodiments of the present disclosure, a center crystal 139 of the groupof nine crystals is configured to direct particles to four adjacentdetectors 142, 144, 146, 148, a second prismatoid 164 of the pluralityof prismatoids is configured to redirect particles between top ends ofanother group of nine crystals of the scintillator array, and the firstprismatoid 162 is substantially adjacent to the second prismatoid 164,and the group of nine crystals 132 is substantially adjacent to theanother group of nine crystals 134. In embodiments of the presentdisclosure, a corner prismatoid of the plurality of prismatoids isconfigured to redirect particles between top ends of a group of fivecrystals of the scintillator array. In embodiments of the presentdisclosure, an edge prismatoid 168 of the plurality of prismatoids isconfigured to redirect particles between top ends of a group of fivecrystals of the scintillator array.

Because the coupling scheme confines intercrystal light sharing to bebetween neighboring SiPMs that enhance crystal identification, one canmatch the index of refraction n between the scintillator columns,prisms, and coupling adhesive to further enhance light sharing andconsequently improve DOI resolution and crystal identification. Allprisms were fabricated using SF10 glass with n=1.767 (instead of BK7with n=1.53, which is the material for the uniform glass light guide)and coupled to the scintillator arrays using NOA170 adhesive with n=1.7.Barium sulfate (BaSO₄) is used as the reflector material between thecrystals and prisms due to its high spatial performance that does notdegrade energy or timing resolutions [21]. SiPM saturation effects,which have been known to positively skew energy resolution andnegatively impact DOI resolution, were not accounted for at this time[22].

FIG. 6 provides perspective views providing details of the prismatoidarray, according to embodiments of the present disclosure.

Perspective views of the prismatoid array, a cross-section of theprismatoid and respective crystals, and individual view of corner, edgeand center prismatoids of a 4-to-1 coupled Prism-PET module are providedin FIG. 6. The bottom ends of a first group of crystals of thescintillator array illustrated in FIG. 6 are configured to directparticles to a first detector of the plurality of detectors, and thebottom ends of a second group of crystals of the scintillator array areconfigured to direct particles to a second detector substantiallyadjacent to the first detector.

FIG. 7 illustrates arrangements of 9-to-1 coupled Prism-PET moduleaccording to embodiments of the present disclosure. The inset of FIG. 7illustrates the predefined readout pattern of each crystal belonging toa single prismatoid light guide in the 9-to-1 coupled module.

FIG. 8 provides perspective views of a light guide array, a prismatoidcrystal array, and a cross-section of the prismatoid of the 9-to-1coupled Prism-PET module according to embodiments of the presentdisclosure.

Advantages are demonstrated using experimental measurements in terms ofcrystal identification, energy resolution, and DOI resolution, includinghow Prism-PET enables up to 9-to-1 crystal-to-readout coupling, whichcan be used to substantially improve spatial resolution withoutincreasing the number of readout channels (FIGS. 7 and 8).

FIG. 9 illustrates a detector readout for 4-to-1 with uniform glass(known configuration). FIG. 10 illustrates a detector readout of 4-to-1coupled Prism-PET module, according to embodiments of the presentdisclosure. FIG. 11 illustrates a detector readout of 9-to-1 coupledPrism-PET module, according to embodiments of the present disclosure.

The detector modules consisted of LYSO crystal arrays fabricated atX-Lum (Shanghai, China) coupled (either 4-to-1 and 9-to-1) to 8×8 arraysof SiPMs (Hamamatsu 513361-3050AE-08). Data acquisition was performedusing TOFPET2 application-specific integrated circuits (ASICs) and aFEB/D v2 readout board from PETsys Electronics. Flood data was acquiredon 4-to-1 and 9-to-1 coupled detector modules with prismatoid lightguide arrays by uniformly exposing the modules with a 3 MBq Na-22 sodiumpoint source (5 mm active diameter). 10,000,000 events from the 4-to-1module and 22,500,000 events from the 9-to-1 module (to acquire an equalnumber of events per crystal) were used for flood histogram generation.

FIG. 12 provides Gaussian histograms and filtered energy spectrums forthe 4-to-1 uniform glass of FIG. 9 (known configuration), the 4-to-1Prism-PET module of FIG. 10, and the 9-to-1 coupled Prism-PET module ofFIG. 11. The upper half of FIG. 12 are 1D Gaussian histograms showingcrystal separation in the x-direction from a corner, edge and centerreadout pixel for the modules of FIGS. 9-11. The bottom half of FIG. 12are filtered energy spectrums with (13%, 9% and 10%) and without (20%,14%, 16%) DOI-correction from a center crystal in FIGS. 9-11.

DOI performance was experimentally measured on a per-crystal basis usinga similar approach described in Ref. [18]. The modules were exposed to aNa-22 source at five different crystal depths (2, 6, 10, 14 and 18 mm)using lead collimation. The source was placed in a lead cylinder with a1 mm pinhole. The pinhole was aligned with the DOI-aligned module on oneside and a single 1.4×1.4×20 mm³ crystal on a reference module on theother side. Coincidence events between the two modules were used toreject scatter events and only accept events along the intended line ofresponse. The histograms for the DOI-estimation parameter [18], w, werecalculated and plotted for all crystals. The w histograms were thenconverted to DOI space using linear regression to determine the slopebetween w and the ground truth DOI, which should be the center of eachGaussian peak. The widths of the Gaussian peaks converted to DOI spacewere used to calculate the DOI resolution of the crystals (FIG.14A-14D). DOI resolution is depth-dependent and equal to the FWHM of theGaussian histograms. Overall crystal-specific DOI resolution wascalculated as the average of the DOI resolutions across the measureddepths [18]. A typical center crystal from each module was used tocalculate the DOI resolutions of each module.

The spatial performance of Prism-PET modules of the present disclosureis characterized compared with standard uniform glass light guide moduleusing flood histograms of fabricated modules (FIGS. 9-11). The glasslight guide module suffers from edge and corner effects, resulting inpoor position-dependent crystal separation. Prism-PET enables excellentcrystal separation throughout the entire detector array without edge andcorner artifacts, which has not previously been achieved in a 4-to-1coupled detector module with single-ended TOF-DOI readout [8,19,20].Similar results are shown with the 9-to-1 coupled Prism-PET module (FIG.11), demonstrating homogenous sub-millimeter crystal separation in aTOF-DOI PET detector module with 3.2×3.2 mm² SiPM pixels. Plotting 1Devent positioning histograms (in the x-direction) confirms thatPrism-PET of the present disclosure has uniform crystal separationperformance at the center, edges and corners. Prism-PET also achieves14% and 16% energy resolution with DOI correction in the 4-to-1 and9-to-1 coupled modules, respectively, whereas the uniform light guideonly achieves 20% energy resolution (FIG. 12, bottom graphs).

For the modules of FIGS. 10 and 11. The histograms of FIGS. 13A-13Cprovide DOI resolution calculated at interaction depths.

FIG. 13A provides DOI resolution in a center crystal of 4-to-1 coupleddetector modules with uniform glass (known configuration).

FIG. 13B provides DOI resolution with prismatoid light guides.

FIG. 13C provides a comparison of DOI resolution based on the lightguide used, showing that the Prism-PET detector module of the presentdisclosure achieves a two-fold improvement in DOI resolution over theuniform glass light guide, as experimentally measured for a singlecenter crystal in each module. The measured DOI resolution for the glasslight guide was 5 mm FWHM, showing strong agreement with previouslyreported results [19]. The Prism-PET modules achieved 2.5 mm FWHM DOIlocalization, the best resolution ever reported using single-endedreadout. Increased depth-dependence of the w parameter is due to 1)controlled and deterministic light sharing pattern within theprismatoids, 2) increased light transfer from scintillators to lightguides due to matched refractive indices, and 3) enhanced deviation ofupward traveling optical photon path by 180° due to the right triangularprism geometry, all of which enhance light sharing between crystalscoupled to the same prismatoid. DOI information can be used to improveboth timing and energy resolution, the former by deconvolvingdepth-specific photon transport inside the scintillator and the latterby constructing depth-specific photopeaks [8,18]. Embodiments of thepresent disclosure achieved 9% and 10% energy resolution in the 4-to-1and 9-to-1 coupled Prism-PET modules, respectively, and 13% energyresolution with the uniform light guide after applying DOI-basedcorrection. Note that the DOI and energy resolution values will slightlychange for better and worse, respectively, after implementing SiPMsaturation correction [22]; as a result, the reported values are moreindicative of the relative performance of Prism-PET of the presentdisclosure compared with the uniform light guide module rather than theabsolute performance in practice.

FIGS. 14A-14D provide DOI resolution graphs, according to embodiments ofthe present disclosure, with conversion from DOI-specific w histogramsto DOI histograms showing the DOI resolution of a single crystal at eachdepth. FIG. 14A provides histograms of the DOI-estimation parameter wacquired at 2, 6, 10, 14 and 18 mm. FIG. 14B provides fit between w andDOI via linear regression. FIG. 14C provides DOI histograms generated bytaking the w histograms in FIG. 14A and multiplying by the slope of thelinear fit in FIG. 14B. FIG. 14D provides DOI resolution at eachacquired depth based on the width of the Gaussians in FIG. 14C.

Perhaps the most important parameter to consider when building a PETsystem is gamma ray detection sensitivity, which is directly related tosignal-to-noise ratio (SNR) and thus determines patient throughput,delivered dose and image quality. Monte Carlo simulations using highlyadvanced software such as GATE are the most reliable way to model andcalculate system-level sensitivity. However, relative improvements insensitivity and comparisons between systems can be done analytically bycalculating (a) geometric sensitivity and (b) sensitivity gain based oncoincidence time resolution (CTR) for time-of-flight readout (TOF),which is equal to the SNR gain squared [24] in Equation (1):

$\begin{matrix}{{{\Delta({SNR})} = \sqrt{\frac{D}{\Delta x}}}{{{\Delta({Sens})} = {{\Delta({SNR})}^{2} = \frac{D}{\Delta x}}},}} & (1)\end{matrix}$

where D is the diameter of the object being imaged and Δx is the lengthof the reconstructed line segment along the line-of-response, which isdirectly proportional to the CTR (Δt) in Equation (2):

$\begin{matrix}{{\Delta x} = \frac{c \star {\Delta t}}{2}} & (2)\end{matrix}$

An example of a dedicated brain PET scanner that can be built withPrism-PET detector modules would be a cylindrical ring with 50 cm axiallength and 25 cm diameter.

FIGS. 15A-15D provide sensitivity graphs, according to embodiments ofthe present disclosure. FIG. 15A provides dimensions and geometriccoverage of a Siemens Biograph Vision, Explorer Total-Body PET scanner,and an example of a Prism-PET brain scanner. FIG. 15B provides geometricsensitivity for a point source positioned in the center of each of thescanners shown in FIG. 15A. FIG. 15C provides relative sensitivity gainas a function of coincidence timing resolution. FIG. 15D provideseffective sensitivity gain calculated as the product between geometricefficiency (as shown in FIG. 15B) and TOF sensitivity gain (as shown inFIG. 15C).

FIG. 15A shows brain Prism-PET scanner dimensions according toembodiments of the present disclosure compared to those of an examplewhole-body (Siemens Biograph Visions) and total-body (Explorer) PETscanner. Having a small ring diameter and large axial field-of-viewgreatly improves the geometric efficiency (FIG. 15B) at the cost ofgreatly increased parallax error and partial volume effect, which can bemitigated by performing depth-of-interaction (DOI) readout [26]. As aresult, small diameter organ-specific scanners should only be built withdetector modules with DOI localization capabilities, such as ourPrism-PET modules.

DOI readout can also be used to recover CTR for TOF readout bydeconvolving the DOI-dependence on coincidence timing (i.e., differencesin path length in optical photons) [8]. Assuming the same CTR reportedas set forth herein (˜150 ps), which is a safe lower bound estimatesince our modules have better DOI resolution (2.5 mm vs. 3 mm),Prism-PET enables a TOF sensitivity gain close to a factor of 10 basedon Eq. (1) when imaging an object with D ˜20 cm such as the human brain(FIG. 15C). The TOF sensitivity gain for human brain imaging is slightlylower for Siemens Biograph Vision, which achieves ˜220 ps CTR [25], andmuch lower for the Explorer (FIG. 15C), which has CTR>400 ps [23].

FIG. 15D shows the overall effective sensitivity gain for human brainimaging when taking both geometric efficiency and TOF sensitivity gaininto account. Based the above calculations, the Prism-PET scanner inembodiments of the present disclosure enables a three-fold and four-foldimprovement in sensitivity compared to the Siemens Biograph Vision andExplorer scanners, respectively.

FIGS. 16A-16F illustrate Compton interaction, according to embodimentsof the present disclosure.

Regarding Compton interaction, Prism-PET of the present disclosureenables Compton scatter energy decomposition (and thus localization) dueto its deterministic light sharing pattern. Let's assume we have a 16×16array of lutetium LYSO crystals with a Prism-PET light guide coupled4-to-1 to an 8×8 array of silicon photomultiplier (SiPM) pixels. Basedon an approximation that each 511 keV gamma rays will produce a signalon 4 different pixels due to light sharing, the light sharing ratiosbetween all crystals belonging to the same prismatoid can be measureddirectly using photoelectric events from flood data. Using thisinformation, the energies of the primary interaction (i.e., recoilelectron) and secondary interaction site (i.e., scattered gamma ray) aredecomposed. Once the decomposed energies are obtained, the twoindependently absorbed events in the scintillation blocks can belocalized and the scattering angles and DOI can be determined. For thePrism-PET module of the present disclosure, identifying a side-by-sideCompton scattering event is possible because of the change from randomlight sharing for photoelectric events to a deterministic pattern (FIGS.16 and 17).

FIGS. 16A-16C provide example of Compton energy decomposition in amulticrystal scintillator array with Prism-PET of the presentdisclosure. FIG. 16D provides examples of light sharing fraction ratiosbetween pixel 1 and neighboring pixels, as labeled in FIGS. 16A-16C. Inone case, both pixels (2 and 4) are adjacent to pixel 1 resulting inequal light sharing fractions, while in the other case pixel 3 isdiagonally across from pixel 1 resulting in a smaller light sharingfraction. (E), (F) Energy and DOI error of Compton interactiondecomposition for Prism-PET.

Classical Compton energy decomposition can be performed as follows. Thetotal absorbed energies EA and EB by the constituent elements A and B(scatter and recoil electron) are given as the summation of the energiesin all 4 SiPMs in Equation (3):

$\begin{matrix}{E_{A} = {\sum\limits_{i = 1}^{4}E_{Ai}}} & (3)\end{matrix}$ ${E_{B} = {\sum\limits_{i = 1}^{4}E_{Bi}}},$

where E_(A1) and E_(B1) are the maximum deposited energies in the SiPMcoupled to the interacted crystal pixels and E_(A2,3,4) and E_(B2,3,4)are the deposited energies in the neighboring columns due to light leakat the bottom (from the SiPM side) and at the top via the prism-mirrorlight guide. The experimental results in FIG. 16A illustrate the fourknown parameters E₁₋₄ corresponding to the detected energies by each ofthe four pixels after the side-by-side Compton scattering event, wherethe total gamma particle energy deposited is provided by Equation (4):

E _(γ) =E _(A) +E _(B)  (4)

Note that the energies of the constituent elements of the Comptonscattering event, namely E_(A1-4) and E_(B1-4), are unknown. Writing theequations based on the measured energies obtains Equation (5):

E1=EA1+EB4

E2=EA2+EB1

E3=EA3+EB2

E4=EA4+EB3,  (5)

providing 4 equations and 8 unknowns. However, the deposited energies inthe neighboring columns are correlated. Considering the inset plot inFIG. 16D where the maximum deposited energy occurred in the top-leftSiPM. Given that the sharing fraction with the three neighbors dependson their proximity to the interacted crystal, and using the Pythagoreantheorem by forming a right triangle using centers of the three neighborsas its vertices, we arrive at Equation (6):

∈₂₄ =d ₁₂ /d ₁₄=1

E _(A4)=∈₂₄ E _(A2) =E _(A2)

∈₂₃ =d ₁₂ /d ₁₃=1/√2=0.7

E _(A3)=∈₂₃ E _(A2)=0.7E _(A2),  (6)

where, for example, d₁₂ is the distance between the centers of theprimary SiPM 1 and neighboring SiPM 2. Substituting Eq. 6 in Eq. 5 weget Equation (7):

E1=EA1+EB2

E2=EA2+EB1

E3=0.7EA3+EB2

E ₄ =E _(A4)+0.7E _(B2),  (7)

where we now have 4 equations and 4 unknowns. Note that in practice thesharing fractions will have spatial variations from the ideal casesshown in Eq. 6 due to some small and unavoidable misalignments betweenthe prism-mirror light guides and the scintillator columns. However, asshown in FIG. 16D, they can be obtained empirically across the array byanalyzing the sharing fractions from individual photoelectric eventsobtained using the flood-histogram experiment.

FIGS. 16B and 16C depict the two decomposed elements of a measuredside-by-side Compton scattering event based on the above analysis.

Given that our modules have DOI localization, we can represent the DOIvariables as Equation (8):

wA=EA1/EA

w _(B) =E _(B1) /E _(B)  (8)

As shown in FIGS. 16E and 16F, the percent error for our estimation of{E_(A1),E_(B1)} and {w_(A),w_(B)} based on 200,000 experimental Gammaevents is −10%. The error can be further reduced using convolutionalneural networks as the estimator specially since we can collect millionsof Gamma events as training dataset using the flood-histogramexperiment.

An example of how a Compton event where the recoil electron andscattered y-ray are fully absorbed in adjacent scintillators in twodifferent SiPMs can be decomposed into its constituent elements can beseen in FIGS. 16A-16D. Calculating the DOI variable w using classicalCompton decomposition resulted in 11% full width at half maximum (FWHM)error (FIG. 16E). In addition, Compton decomposition results in 15% FWHMenergy error (FIG. 16F).

FIG. 17 illustrates photoelectric and Compton interaction, according toembodiments of the present disclosure, in which graphs of random lightsharing pattern of a glass light guide are provided above graphs ofdeterministic light sharing pattern of Prism-PET of embodiments of thepresent disclosure. FIG. 17 shows that experimental results of severalexamples of Compton events absorbed in adjacent crystals in a Prism-PETmodule of the present disclosure vs. a module with a flat glass lightguide.

The light sharing pattern in the glass light guide module is random,making it difficult (and in most cases, impossible) to decompose thedetected energies into the constituent energies of the scattered photonand recoil electron. Due to the right triangular prism geometry, thelight sharing pattern is deterministic in the Prism-PET module, makingit practical to decompose the event into its constituent energies basedon the known light sharing ratios between crystals.

Accordingly, a particle detector is provided that includes ascintillator array comprising a plurality of scintillator crystals; aplurality of detectors provided on a bottom end of the scintillatorarray; a plurality of prismatoids provided on a top end of thescintillator array; and at least one processor in operativecommunication with the plurality of detectors. The at least oneprocessor comprises a plurality of supervised machine learningalgorithms, including convolutional and regressive networks, configuredto perform 3D gamma ray localization of at least one interaction sitewithin at least one scintillator crystal of the plurality ofscintillator crystals. The at least one processor is configured torecover at least one Compton event scattering among the plurality ofscintillator crystals, and localize the at least one Compton event at ascintillator level based on 3D gamma ray localization. The at least oneprocessor is further configured to determine a scatter angle based on atleast one Compton event and DOI information. The at least one processoris further configured to localize at least one Compton event based ondecomposed energies of at least two interactions absorbed in theplurality of scintillator crystals, with the decomposed energies basedon at least one light sharing pattern and the at least one light sharingpattern being based on positions of the plurality of scintillatorcrystals relative to the plurality of detectors and the plurality ofprismatoids.

According to embodiments of the present disclosure, the at least onelight sharing pattern is mapped based on light sharing ratios betweenscintillator crystals of a same prismatoid; the light sharing ratios arebased on a predefined geometry of at least one prismatoid of theplurality of prismatoids; the mapping is based on measured photoelectricevents, decomposed energies of at least one primary interaction and atleast one secondary interaction, and the at least one primaryinteraction is based on electron recoil and the at least one secondaryinteraction is based on gamma ray scattering, with the light sharingpattern being deterministic.

Accordingly, a cost-effective and practical method for achieving highspatial and DOI resolution in multicrystal single-ended readout detectormodules is provided without introducing edge and corner artifacts.Embodiments of the present disclosure can be used to enabledepth-encoding in clinical whole-body and total-body PET scanners [23]without increasing cost (prismatoid light guide array comprises lessthan 10% of the total cost of each Prism-PET module) and powerconsumption, while improving spatial resolution (via 9-to-1 coupling of,for example, 2×2×20 mm³ crystals to 6×6 mm² readout pixels), sensitivity(via intercrystal Compton scatter recovery), and timing resolution (viaDOI-correction of timing jitter). For small ring-diameter brain imaging,the 9-to-1 coupling ratio enables sub-millimeter spatial resolution,while extending axial field-of-view to about double that of whole-bodyPET scanners enables the same geometric sensitivity gain as the Explorertotal-body PET scanner (FIG. 15) [8, 23-26]. In addition, having 2.5 mmDOI resolution greatly mitigates parallax error and potentially enablesachieving ˜100 ps coincidence time resolution via DOI-correction [8],which would enable even higher sensitivity and spatial resolution[24-26]. These benefits yield a practical, cost-effective, and powerefficient approach to achieving both high spatial resolution and highsensitivity at relatively low dose for quantitative in vivo functionaland molecular imaging of many human body organs, including importantstructures of the brain that have not been resolvable with existing PETscanners such as the raphe nuclei, cholinergic basal forebrain nuclei,Locus coeruleus and hypothalamic nuclei, all of which are thought toplay crucial roles in basic physiology as well as in the pathophysiologyof common neurodegenerative and psychiatric disorders [26-30]. Theability to visualize and quantitate these and similar targets has thepotential to revolutionize molecular imaging in both the clinical andresearch arenas, providing hitherto unavailable tools for earlydiagnosis and basic research in oncology and brain disorders.

Another advantage of embodiments of the present disclosure is theability to more accurately identify the initial interaction site ofCompton scatter events, further improving spatial resolution andsensitivity (FIGS. 16-17). Traditionally, Compton detection has beenperformed using multiple detector layers, but a recent paper outlinedthe criteria for localizing and decomposing Compton interactions usingsingle-ended readout, citing high resolution DOI readout as a keyfeature for Compton scatter recovery [31]. A uniform light guide is notoptimal for this task because the SiPM pattern of individual events israndom, whereas our Prism-PET modules create a deterministic lightsharing pattern regardless of the interaction location inside theprimary scintillator column (FIGS. 1-4 and 14). Notably, Prism-PETenables the decomposition of side-by-side scattered photon and recoilelectron events, which are the most probable and most difficult toanalyze scattering events, into their constituent energies, spatiallocation, and DOI. Compton scatter recovery is especially critical toretain high sensitivity in detector modules with small scintillatorcrystals since the scattered photon is more likely to be absorbed in adifferent crystal from the primary interaction site as crystal sizedecreases [32].

Embodiments of the present disclosure provide a Prism-PET detectormodule which is a true single-ended analogy of a dual-endeddepth-encoding readout using efficient 180° light bending reflectors forenhanced light sharing. A 2.5 mm FWHM DOI resolution is achieved and upto 9-to-1 scintillator to SiPM coupling for high spatial resolutionwhile directly coupling the crystal array to the SiPM pixels to minimizelight leakage and retain high photon detection efficiency, which isrequired for good timing resolution. The top side reflector is comprisedof an optimized pattern of segmented prismatoid light guides forefficient redirection of scintillation photon paths from the primarycrystal to selected nearest-neighboring SiPMs, thus mimicking veryclosely the operation of dual-ended readout detectors. This creates ananisotropic and deterministic pattern of signal that can be used todecompose a side-by-side Compton scattering events into theirconstituent energy and DOI information for the purpose of scatterrecovery. Thus, high and uniform spatial resolution are achieved (9-to-1coupling of −1 mm crystals; absence of edge and corner artifacts due toenhanced light sharing; reduced spatial blur due to Compton-scatteredphotons via scatter recovery), high sensitivity is achieved (20-mm thickdetectors, and intercrystal Compton scatter recovery), and good energyand timing resolutions are achieved (especially after applyingDOI-correction) in compact systems (DOI encoding eliminates parallaxerror and permits smaller ring-diameter). With these unique combinationsof features, cost-effective and compact TOF-DOI-Compton PET scannerscould be developed based upon Prism-PET modules for small animal andhuman organ-specific functional and molecular imaging.

While the invention has been shown and described with reference tocertain aspects thereof, it will be understood by those skilled in theart that various changes in form and details may be made therein withoutdeparting from the spirit and scope of the present invention as definedby the appended claims and equivalents thereof. No recitation of anyclaim set forth below is to be construed as a means plus functionelement without express use of “means for” or “step for.”

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What is claimed is:
 1. A particle detector, comprising: a scintillatorarray comprising a plurality of scintillator crystals; a plurality ofdetectors provided on a first end of the scintillator array; a pluralityof prismatoids provided on a second end of the scintillator array; andat least one processor in operative communication with the plurality ofdetectors, wherein the at least one processor comprises a plurality ofsupervised machine learning algorithms configured to perform threedimensional (3D) gamma ray localization of at least one interaction sitewithin at least one scintillator crystal of the plurality ofscintillator crystals.
 2. The particle detector of claim 1, wherein theat least one processor is further configured to recover at least oneCompton event scattering among the plurality of scintillator crystals,and localize the at least one Compton event at a scintillator levelbased on 3D gamma ray localization.
 3. The particle detector of claim 1,wherein the at least one processor is further configured to determine ascatter angle based on at least one Compton event and depth ofinteraction (DOI) information.
 4. The particle detector of claim 1,wherein the at least one processor is further configured to localize atleast one Compton event based on decomposed energies of at least twointeractions absorbed in the plurality of scintillator crystals.
 5. Theparticle detector of claim 4, wherein the decomposed energies are basedon at least one light sharing pattern.
 6. The particle detector of claim5, wherein the at least one light sharing pattern is based on positionsof the plurality of scintillator crystals relative to the plurality ofdetectors and the plurality of prismatoids.
 7. The particle detector ofclaim 5, wherein the at least one light sharing pattern is mapped basedon light sharing ratios between scintillator crystals of a sameprismatoid.
 8. The particle detector of claim 7, wherein the lightsharing ratios are based on a predefined geometry of the sameprismatoid.
 9. The particle detector of claim 7, wherein the mapping isbased on measured photoelectric events, decomposed energies of at leastone primary interaction and at least one secondary interaction, andwherein the at least one primary interaction is based on electron recoiland the at least one secondary interaction is based on gamma rayscattering.